Predictive Elements of Trauma and Its After-effects: Importance of the Quality of Neurobiological Response to Stress

Stress Reaction Clinical Trial

— LIFT-UP  

Official title:

Predictive Elements of Trauma and Its After-effects: Importance of the Quality of Neurobiological Response to Stress

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04530214
• Other study ID #: 2018PPRC30
• Secondary ID: 2019-A01811-56
• Status: Recruiting
• Start date: November 4, 2020
• Est. completion date: May 2023

Study information

• Verified date: April 2023
• Source: Direction Centrale du Service de Santé des Armées
• Contact: Anaïs DUFFAUD
• Phone: 178651315
• Email: anais.duffaud[@]intradef.gouv.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The neurobiological response to stress is an adaptive response allowing us to cope with the multiple aggressions of daily life. This response orchestrates the body's systemic reaction. The intensity of response to stress can modify the body's functioning, which implies a variety of fields where biomarkers may be isolated: immunity, psychology, neurophysiology, integrative physiology. When stress is too intense or prolonged, response to stress may become misfitted and deleterious.

This study is based on the hypothesis that a severe physical or psychological trauma is associated with an intense and misfitted stress that is responsible from an undue immuno-inflammatory activation (through sympathetic activation). The result is a subinvasive state of systemic and tissue inflammation (low-noise inflammation), responsible for the mid-term deleterious consequences of the traumatic event.

The objective of this study is to understand how the dysregulation of intense stress simultaneously generates an initial pathological state and an alteration of mid-term evolution (which is considered as a poor prognosis and/or as responsible for after-effects).

The investigators wish to identify relevant biomarkers of the mechanisms activated during intense stress and influencing the immuno-inflammatory and epigenetic spheres with deleterious consequences on physiological and psychological functions.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: May 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

Inclusion Criteria:

• Fracture of the upper end of the femur

• Cognitive state allowing the understanding of questionnaires

Exclusion Criteria:

• Traumatic Brain Injury

• Chronic inflammatory or immune pathologies

• On anticoagulants

• On neuroleptic or antidepressant treatment

• Pathology or health condition not allowing 1-year survival

Related Conditions & MeSH terms

• Fractures, Stress
• Stress Reaction

Intervention

Other:
• Blood collection
Blood collection at enrollment (before surgery) and at Visit 1 (45-60 days following surgery)
• Saliva collection
Saliva collection at enrollment (before surgery) and at Visit 1 (45-60 days following surgery)
• Electrocardiography (ECG)
Electrocardiography (ECG) at enrollment (24-72h following surgery) and at Visit 1 (45-60 days following surgery) to assess heart rate variability

Behavioral:
• Questionnaires
Mental health assessment through questionnaires at enrollment (24-72h following surgery), at Visit 1 (45-60 days following surgery), at Visit 2 (7 months following surgery) and at Visit 3 (12 months following surgery)

Locations

Country	Name	City	State
France	CHU Pellegrin	Bordeaux
France	Hôpital d'Instruction des Armées Percy	Clamart
France	Hôpital d'Instruction des Armées Bégin	Saint-Mandé
France	Hôpital d'Instruction des Armées Sainte-Anne	Toulon

Sponsors (1)

Lead Sponsor	Collaborator
Direction Centrale du Service de Santé des Armées

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of depression	Screening for depression will be done using a validated self-report questionnaire, the Geriatric Depression Scale Short Version (GDS).; We will use the threshold value of 10 (score > or =) which corresponds to a very high probability of depression.	12 months following surgery
Primary	Occurrence of "psychosomatic death"	The diagnosis of "psychosomatic death" will be made by a physician. There is no consensus on the diagnosis of this syndrome. However, a patient with "psychosomatic death" is likely to be hospitalized or followed up medically and will not be able to respond to the investigator's request for a telephone interview.	12 months following surgery
Primary	Occurrence of death	Vital status will be collected from the participant's family or referring physician or at the birth & death record service (of the participant's town)	12 months following surgery
Secondary	Evolution of heart rate variability between enrollment and Visit 1	Heart rate variability will be assessed using electrocardiography recordings	Between enrollment and Visit 1 (45-60 days following surgery)
Secondary	Evolution of perceived stress level between enrollment and Visit 1	Perceived stress level will be assessed with the Perceived Stress Scale (PSS). Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress.	Between enrollment and Visit 1 (45-60 days following surgery)
Secondary	Evolution of anxiety level between enrollment and Visit 1	Anxiety level will be assessed with the French version of Spielberger's State-Trait Anxiety Inventory adapted for people aged 65 and older (IASTA-Y65+).; Individual scores on the IASTA-Y 65+ can range from 20 to 80 with higher scores indicating higher anxiety.	Between enrollment and Visit 1 (45-60 days following surgery)
Secondary	Evolution of post-traumatic stress disorder severity level between enrollment and Visit 1	Post-traumatic stress disorder severity will be assessed with the Post-traumatic stress disorder CheckList for DSM-5 (Diagnostic and Statistical Manual Diploma in Social Medicine) (PCL-5) scale. Individual scores on the PCL-5 can range from 0 to 80 with higher scores indicating higher post-traumatic stress disorder severity.	Between enrollment and Visit 1 (45-60 days following surgery)
Secondary	Evolution of quality of life between enrollment and Visit 1	Quality of life will be assessed using the abbreviated version of the World Health Organization Quality of Life (WHOQOL-Bref).; The WHOQOL-Bref is grouped into 4 domains : Physical health (score range from 7 to 35); Psychological health (score range from 6 to 30); Social relationships (score range from 3 to 15); Environment (score range from 8-40) Higher scores indicate higher quality of life.	Between enrollment and Visit 1 (45-60 days following surgery)
Secondary	Evolution of cortisol level between enrollment and Visit 1	Cortisol level will be measured in saliva sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Secondary	Evolution of GABA level between enrollment and Visit 1	Gamma-aminobutyric acid (GABA) level will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Secondary	Evolution of oxydative stress level between enrollment and Visit 1	Oxydative stress level will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Secondary	Evolution of BDNF level between enrollment and Visit 1	Brain-derived neurotrophic factor (BDNF) level will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Secondary	Evolution of pro and anti-inflammatory cytokines level between enrollment and Visit 1	Cytokines level will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Secondary	Evolution of IGF-1 level between enrollment and Visit 1	Insulin like growth factor type 1 (IGF-1) will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Secondary	Evolution of NPY level between enrollment and Visit 1	Neuropeptide Y (NPY) level will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Secondary	Evolution of NPS between enrollment and Visit 1	Neutrophil-platelet score (NPS) will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Secondary	Evolution of ocytocin level between enrollment and Visit 1	Ocytocin level will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Secondary	Evolution of methylation of genes coding for BDNF between enrollment and Visit 1	Methylation of genes coding for BDNF will be measured on DNA extracted from blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Secondary	Evolution of methylation of genes coding for glucocorticoid receptors between enrollment and Visit 1	Methylation of genes coding for glucocorticoid receptors will be measured on DNA extracted from blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)